Introduction

Gas gangrene caused by Clostridium species is a complication of contaminated deep wounds that has been known for a long time [1]. Some species are highly pathogenic in humans and produce toxins associated with severe syndromes. Previously reported cases of orbital clostridia infection that causes gas gangrene were caused by Clostridium perfringens [2–4]. Although Clostridium septicum infections are responsible for 1.3 % of all clostridia infections [5, 6], reviewing the literature the authors have found only five cases of C. septicum panophthalmitis [7–11] and no report on orbital involvement without intraocular inflammation.

Case report

An 86-year-old woman was referred to our ophthalmology department from the internal medicine emergency room with unilateral exophthalmia and diplopia that had developed over the past month. The best corrected visual acuity was 0.5 in the right eye and 0.8 in the left one. The palpebral fissure could be closed. Anaemia should be highlighted in her past medical history that has been known for 2 years [red blood cell (RBC), 3.2–3.39 × 1012/L; hematocrit (HTC), 25.9–27.7 %], but the etiology was unknown as the patient refused to undergo the necessary examinations. Orbital CT revealed a space-occupying, well-defined lesion of 27 × 14 mm in size with mixed density and contrast accumulation in the right orbit (Fig. 1). The patient did not consent to surgery or biopsy; therefore, she was discharged on her own request.

Fig. 1
figure 1

On first admission, the orbital CT revealed a space-occupying, well-defined lesion of 27 × 14 mm in size with mixed density (arrow), and contrast accumulation in the right orbit. It dislocated the bulbus forward

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One year later, due to excessive pain and inflammatory signs of the right orbit for 5 days, she was readmitted to our department. The right bulbus had no light perception, it was displaced temporally (i.e. toward the temple) and downward, and was unable to move. The palpebral fissure was not able to close. The bulbar conjunctiva was chemotic with localized necrosis, and the cornea was swollen and rough with erosion (Fig. 2), but in the anterior chamber neither hypopyon nor a gas bubble was visible. Owing to the status of the cornea, the posterior segment could not be examined, but no signs of intraocular inflammation were detected by ultrasound scan. The orbital CT clearly revealed a cyst, laterally, with a maximum diameter of 35 mm filled with an air-like substance with some dense fluid intensity and calcified areas in the centre and contrast accumulation in these areas. The retrobulbar fat tissue was infiltrated, but the bony orbital walls were not. The lateral muscle was indistinguishable (Fig. 3). After a 5-day course of switching her from acenocoumarol to low molecular weight heparin, a microbiological sample was taken from the abscess, and biopsy was performed from the orbital mass. During this period, because of the signs of orbital inflammation, 2 × 500 mg ciprofloxacin (Ciprobay®, Bayer Pharma AG, Germany), 1 × 2 g ceftriaxone (Rocephine®, Roche, Hungary) and 2 × 500 mg metronidazole (Klion®, Richter Gedeon, Hungary) were administered preoperatively, and after the surgery, empirical 2 × 1.2 g amoxicillin + clavulanic acid (Augmentin Duo® GlaxoSmithKline, UK) and 3 × tobramycin + dexamethasone (Tobradex®, Alcon, USA) ointment were applied for 2 weeks, which resulted in the cessation of the inflammation. On microbiological examination from the surgical sample, Gram-positive rod-shaped bacteria were visible, and C. septicum was cultured (susceptible for penicillin, amoxicillin + clavulanic acid, clindamycin, cefoxitin, imipenem and metronidazole). As the patient had no fever or signs of a severe systemic infection, no blood culture was performed. The biopsy revealed indolent B cell lymphoma (CD20+, CD5−, CD10−) with clonal IgH gene rearrangement.

Fig. 2
figure 2

On second admission, prior to surgery, the right bulbus was without light perception, displaced temporally and downward, and unable to move. The palpebral fissure could not be closed, the eyelid was swollen, the conjunctiva was highly chemotic, and the cornea was swollen, and rough with erosion

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Fig. 3
figure 3

Orbital CT showed laterally an air-containing intensity mass with a maximum diameter of 35 mm with some dense fluid and calcified areas towards the centre with corresponding contrast accumulation in these areas (arrow). The lateral muscle could not be distinguished. It infiltrated the retrobulbar fat tissue but not the orbital wall

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The following basic laboratory findings were noteworthy: higher white blood cell, 13.31 × 109/L; neutrophil, 83.1 %; C-reactive protein, 112.2 mg/L; and tumour markers such as carcinoembryonic antigen, 32.1 μg/L and Ca-125, 68.6 kU/L. Furthermore lower lymphocyte, 6.6 %; RBC, 3.39 × 1012/L; haemoglobin, 78 g/L; HCT, 25.9 % and albumin, 35 g/L values should be highlighted.

Although she had mild atherosclerosis with a previous acute myocardial attack, it did not cause alteration in the blood flow by Doppler ultrasonography.

Consecutive abdominal ultrasound, that was performed due to lack of appetite and slimming, revealed a large ascending colon–caecum neoplasm (120 × 50 × 45 mm) with a lobulated contour, and this was re-evaluated by CT in the late post-operative period. An irregularly thickened segment of the ascending colon of approximately 8 cm in length was visualised. At its proximal end, the fat tissue was infiltrated to a 5–6-mm depth, and it had a short segment lying on the psoas muscle. In the mesentery, near the ascending colon, several 8–10-mm nodules were reflected in the lymphatic nodes. Surgery of the tumour and, therefore, biopsy were not performed owing to the advanced stage of the tumour. Ten weeks after the ophthalmic surgery, the patient died in exsiccosis caused by diarrhoea. No autopsy was performed, as the patient’s family vetoed it.

Discussion

Clostridial disease syndromes can roughly be categorized as neurotoxic (C. tetani, C. botulinum), enterotoxic (C. difficile, C. perfringens) and histotoxic (C. perfringens, C. septicum) [6].

C. perfringens infections following a penetrating injury of the orbit have been discussed [3, 12–14], but on overviewing the literature, we found no reference to C. septicum gas gangrene in an orbital localization without endophthalmitis.

C. septicum is a rod-shaped saprophytic bacterium which is anaerobic, Gram positive and reproduces by forming spores [15]. Production of the cytolytic alpha toxin by this pathogen is an essential virulence factor by inducing cell membrane permeability through pore formation [16, 17]. Besides alpha toxin, it produces delta toxin (alpha-haemolysin), and at least one other haemolysin, a desoxyribonuclease, a hyaluronidase, and a fibrinolysin [5, 18, 19].

C. septicum infections are known to coexist with malignancies, and it is thought that a portal of entry for the bacteria develops from the disruption of the normal mucosal barrier caused by mucosal ulceration of the tumour surface and the haematogenous invasion [15]. Leukaemia and lymphoproliferative disorders, especially when under treatment with chemotherapy or radiotherapy, are second only to colon cancer as predisposing factors [1].

Autopsy studies have implicated the distal ileum or caecum as the portal of entry in 60 % of patients with C. septicum bacteraemia with caecitis or distal ileitis having been present in 65 % of these individuals [20]. Underlying conditions that might be associated with vascular compromise, such as diabetes or peripheral vascular disease, have frequently been implicated [1]. In the absence of an obvious portal of entry, isolation of C. septicum or other clostridia in the blood or tissues coupled with gas gangrene should suggest a covert tumour. C. septicum sepsis is often fulminant with reported mortality rates of approximately 60 % [17].

Early detection, massive antibiotic therapy, and surgery may decrease the extremely high morbidity and mortality rate associated with these infections [15].

The optimal treatment of gas gangrene has not been determined, although surgical debridement in conjunction with antibiotics and hyperbaric oxygen are recommended [21, 22]. Animal studies of C. septicum gangrene have not been reported. According to in vitro data [1], unlike C. perfringens, C. septicum is susceptible to penicillin (10–25 million units/day), tetracycline, erythromycin, clindamycin, chloramphenicol, and metronidazole, so there appear to be several options for antibiotic selection [1, 23].

In our patient, tumour of the colon and caecum was present; and she had a B cell lymphoma. Inconsistent with previous reports, no aortal aneurism or diabetes was present, and the mild atherosclerosis may have been the only vascular association. Bacteraemia did not manifest, but haematogenic spread to the orbit occurred. As no biopsy was performed at the first ophthalmologic presentation, it is uncertain, but possible that a lymphoma metastasis was formed in the orbit, and the clostridia gas gangrene was secondary to the predisposing conditions of the malignancy. The calcified areas in the abscess may have been caused by previous bleeding. Unfortunately, autopsy was not performed; therefore, no classification of the tumour was possible. Although, C. septicum infection has a high mortality and rapid course, it is likely that the infection healed, and the patient died as the consequences of the tumour.

Ophthalmologists should consider the following: in case of any radiologically detected mass in the orbit, biopsy should be considered, and the patient should be convinced of its importance. Even in indolent lymphoma, consecutive examinations might discover a further type of malignancy. Spontaneous gas gangrene in the absence of trauma is a rare entity. If it is caused by C. septicum, further examinations are needed to search for a covert tumour, primarily located in the intestinal tract. Despite the high fatality rate, surgical debridement and antibiotic treatment might be beneficial.